Copyright 2004 AScribe Inc.
May 5, 2004 Wednesday
LENGTH: 974 words
HEADLINE: Gene Therapy Reduces Drinking in Rats With Genetic Predisposition to
'Alcoholism'; Finding Confirms Earlier Result Using Better Model for Human Alcohol
UPTON, N.Y., May 5 [AScribe Newswire] -- As a follow up to previous work showing
that gene therapy can reduce drinking in rats trained to prefer alcohol, scientists
at the U.S. Department of Energy's Brookhaven National Laboratory have used the
same technique to cut drinking in rats with a genetic predisposition for heavy
alcohol consumption. The findings, along with additional results on the effects
of long-term ethanol consumption on certain aspects of brain chemistry, are published
in the May 2004 issue of Alcoholism Clinical and Experimental Research.
"Though we are still early in the process, these results improve our understanding
of the mechanism or mechanisms of alcohol addiction and strengthen our hope that
this treatment approach might one day help people addicted to alcohol," said
Panayotis [Peter] Thanos, who lead the study in Brookhaven Lab's medical department.
Genetically predisposed alcohol-preferring rats are a much better model for human
alcoholism than the rats used previously, which the scientists had to train to
prefer alcohol. Without any training, the genetic alcohol-preferring rats drink,
on average, more than five grams of ethanol per kilogram of body weight per day
when given a free choice between alcohol and plain water.
Genetically non-preferring rats, in contrast, typically consume less than one
gram of ethanol per kilogram of body weight per day.
In this study, both groups were treated with gene transfer to increase the level
of a brain receptor for dopamine, a chemical important for transmitting feelings
of pleasure and reward and known to play a role in addiction. After the gene treatment,
the alcohol preferring rats exhibited a 37 percent reduction in their preference
for alcohol and cut their total alcohol consumption in half -- from 2.7 grams
per kilogram of body weight before treatment to 1.3g/kg after.
Non-preferring rats also reduced their drinking preference and intake after gene
treatment, but not in nearly as dramatic a fashion. The greatest reductions in
alcohol preference and consumption were observed within the first few days after
gene treatment, and both preference and consumption returned to pre-treatment
levels by day 20.
The gene administered was for the dopamine D2 receptor, a protein shown in various
studies to be relevant to alcohol and drug abuse. For example, low levels of dopamine
D2 receptors in the brain have been postulated to lead to a reward deficiency
syndrome that predisposes certain people to addictive behaviors, including drug
and alcohol abuse. The alcohol-preferring rats used in this study have about 20-25
percent lower levels of dopamine D2 receptors when compared to the non-preferring
rats, which may, in part, explain their tendency toward heavy drinking.
The scientists delivered the gene by first inserting it into a virus that had
been rendered harmless. They then injected the virus directly into the rats' nucleus
accumbens, the brain's pleasure center. The idea behind this type of gene therapy
is to use the virus as a vector to carry the gene to the brain cells, which can
then use the genetic instructions to make the D2 receptor protein themselves.
As an additional measure in this study, the scientists used micro-positron emission
tomography [microPET] imaging to non-invasively assess the effects of chronic
alcohol consumption on D2 receptor levels in alcohol-preferring and non-preferring
rats. They measured D2 levels seven weeks after the gene therapy treatment [well
after the effects of gene therapy had worn off]. D2 receptor levels in alcohol-preferring
rats were significantly lower [about 16 percent] compared to that in non-preferring
rats. These levels were similar to previous data in nave preferring and non-preferring
In future studies, the D2 connection to alcoholism will be examined in transgenic
mice that are totally depleted of D2. In addition, the scientists plan to develop
a second generation D2 vector approach that will provide a longer period of treatment.
"These findings further support our hypothesis that high levels of D2 are
causally associated with a reduction in alcohol drinking and may serve as a protective
factor against alcoholism," Thanos said.
This study was funded by the Office of Biological and Environmental Research within
the Department of Energy's Office of Science and by the
National Institute of Alcohol Abuse and Alcoholism within the National
Institutes of Health.
One of the ten national laboratories overseen and primarily funded by the Office
of Science of the U.S. Department of Energy [DOE], Brookhaven National Laboratory
conducts research in the physical, biomedical, and environmental sciences, as
well as in energy technologies and national security. Brookhaven Lab also builds
and operates major scientific facilities available to university, industry and
government researchers. Brookhaven is operated and managed for DOE's Office of
Science by Brookhaven Science Associates, a limited-liability company founded
by Stony Brook University, the largest academic user of Laboratory facilities,
and Battelle, a nonprofit, applied science and technology organization. Visit
Brookhaven Lab's electronic newsroom for links, news archives, graphics, and more:
BNL Media Relations: Karen McNulty Walsh, 631-344-8350, firstname.lastname@example.org
Peter Genzer, 631-344-3174, email@example.com
Previous related study:
An electronic version of this news release, with pictures, can be
Note: Peter Thanos lives in Port Jefferson, New York.
Karen McNulty Walsh, 631-344-8350, firstname.lastname@example.org
Peter Genzer, 631-344-3174, email@example.com
LOAD-DATE: May 6, 2004